Esophageal cancer is a common malignancy with a very poor prognosis. The principal reason for the poor prognosis is that most tumors are asymptomatic and go undetected until they have spread beyond the esophageal wall and are unresectable. Significant reduction in esophageal cancer mortality will require successful strategies to diagnose a greater proportion of cases at earlier, more curable stages of disease. A successful early detection program for esophageal cancer will require an accurate, patient-acceptable screening test, confirmatory tests that can localize precursors and early invasive lesions, and a curative therapy that is acceptable to asymptomatic patients. This project includes four studies, each designed to evaluate a technique which may be useful in such an early detection program: a. The Cytology Sampling Study will estimate and compare the sensitivity of the two currently available cytological sampling techniques, the Chinese balloon and the Japanese encapsulated sponge, for identifying biopsy-proven squamous dysplasia and cancer of the esophagus. b. The Mucosal Staining Study will evaluate whether mucosal iodine staining can improve endoscopic localization of esophageal squamous dysplasia and cancer. c. The Endoscopic Ultrasonography Study will evaluate how accurately ultrasonography can identify and stage squamous dysplasia and early invasive cancer of the esophagus. d. The Endoscopic Therapy Pilot Study will evaluate the feasibility, safety, acceptability, and preliminary efficacy of mucosectomy, a focal endoscopy therapy which has recently been developed in Japan. Currently, standard treatment for early esophageal cancer is esophagectomy, a large operation that is not acceptable to many asymptomatic patients. For an early detection program to decrease esophageal cancer mortality, we must develop an alternative cure that is acceptable to such patients. This project will be carried out in Linxian, China, a county with extraordinary rates of esophageal cancer and a correspondingly high prevalence of the asymptomatic precursor and early invasive lesions that are needed for these studies. The project will be a collaborative effort of investigators from the National Cancer Institute, the Cancer Hospital of the Chinese Academy of Medical Sciences, Georgetown University, and the University of California at Los Angeles.